Heart disease and high blood pressure affect over 20 million Americans and much of this is caused by the disease state essential hypertension. In order to understand and to treat part of the cause of this disease, the synthesis of rigid derivatives for study as alpha and beta adrenergic antagonists is under investigation. The work of Bentley in the morphine series has demonstrated that rigid analogs can be much more active than mobile compounds and more stereoselective. The rigid structures under study contain important biofunctionality for antihypertensive activity constrained in a rigid framework. It is felt this will permit blockade of one set of alpha, beta-1 or beta-2 receptors without affecting the other two thus leading to much needed cardioselective and chronoselective agents. Since the derivatives under study are not free to rotate, the geometry and stereochemistry necessary for exact fit to beta receptors can be determined. In the past this has been impossible for the drugs which were mobile and no one knew exactly what conformation was maintained in the drug-receptor complex. Structure-activity profiles of these analogs will provide accurate information on the geometry of the drug in the drug-receptor complex which can be extrapolated to determine the geometry of the beta receptor sites. The final outcome will be selective, orally active, antihypertensive agents for treatment of essential hypertension with few side effects. BIBLIOGRAPHIC REFERENCES: "Reactions of 1,2 and 1,3 Dicarbonyl Compounds with Dimethyl Beta-Ketoglutarate I. Synthesis of Methyl 5,6,7,8-Tetrahydro-5-oxocoumarine delta4 (3H), alpha-acetate," D. Yang, J. Oehldrich, D. Foerst, and J. Cook, J. Org. Chem., 41(4), 743 (1976). "Reactions of Dicarbonyl Compounds with Dimethyl Beta-Ketoglutarate II. Simple Synthesis of Compounds of the (10.3.3) and (6.3.3) Propellane Series," D. Yang and J. M. Cook, J. Org. Chem., 41, 1903 (1976).